R-based reproduction of the estimation process hidden behind NONMEM(R) Part 1: first-order approximation method

ABSTRACT

NONMEM(R) is the most-widely used nonlinear mixed effects modelling tool introduced into population PK/PD analysis. Even though thousands of pharmaceutical scientists utilize NONMEM(R) routinely for their data analysis, the various estimation methods implemented in NONMEM(R) remain a mystery for most users due to the complex statistical and mathematical derivations underlying the algorithm used in NONMEM(R). In this tutorial, we demonstrated how to directly obtain the objective function value and post hoc eta for the first order approximation method by the use of R. We hope that this tutorial helps pharmacometricians understand the underlying estimation process of nonlinear mixed effects modelling.